STI571 Plus Cytarabine in Treating Patients With Chronic Myelogenous Leukemia

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00015834
First received: May 6, 2001
Last updated: January 23, 2013
Last verified: January 2013
  Purpose

Phase I/II trial to study the effectiveness of combining STI571 and chemotherapy in treating patients who have chronic myelogenous leukemia. Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. STI571 may stop the growth of leukemia cells. Combining chemotherapy and STI571 may kill more cancer cells


Condition Intervention Phase
Blastic Phase Chronic Myelogenous Leukemia
Chronic Myelogenous Leukemia, BCR-ABL1 Positive
Relapsing Chronic Myelogenous Leukemia
Drug: imatinib mesylate
Drug: cytarabine
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I/II Trial of STI571 and High-Dose Cytarabine in Myeloid Blast Crisis of Chronic Myeloid Leukemia

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Toxicity according to NCI/NIH Common Toxicity Criteria [ Time Frame: Up to 2 years ] [ Designated as safety issue: Yes ]
    Described by duration, relatedness to treatment, and action taken.

  • Hematologic response [ Time Frame: Up to 6 months ] [ Designated as safety issue: No ]
  • Bone marrow cytogenetic response [ Time Frame: Up to 6 months ] [ Designated as safety issue: No ]

Enrollment: 46
Study Start Date: May 2001
Primary Completion Date: April 2003 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (imatinib mesylate, cytarabine)
Patients who have not previously received imatinib mesylate receive oral imatinib mesylate daily on days 1-35. Patients who have previously received imatinib mesylate for at least 28 days receive oral imatinib mesylate on days 22-35. All patients receive cytarabine IV over 2 hours every 12 hours on days 29-32. Patients with more than 5% residual blasts in bone marrow on day 28 receive a second course in the absence of disease progression or unacceptable toxicity.
Drug: imatinib mesylate
Given PO
Other Names:
  • CGP 57148
  • Gleevec
  • Glivec
Drug: cytarabine
Given IV
Other Names:
  • ARA-C
  • arabinofuranosylcytosine
  • arabinosylcytosine
  • Cytosar-U
  • cytosine arabinoside

Detailed Description:

OBJECTIVES:

I. Determine the maximum tolerated dose of high-dose cytarabine when combined with imatinib mesylate in patients with blastic phase chronic myelogenous leukemia.

II. Determine the safety of this regimen in these patients. III. Determine the pharmacokinetics of this regimen in these patients. IV. Determine the frequency of hematologic and cytogenetic responses, duration of response, and survival of patients treated with this regimen.

OUTLINE: This is a multicenter, dose-escalation study of cytarabine.

Phase I: Patients who have not previously received imatinib mesylate receive oral imatinib mesylate daily on days 1-35. Patients who have previously received imatinib mesylate for at least 28 days receive oral imatinib mesylate on days 22-35. All patients receive cytarabine IV over 2 hours every 12 hours on days 29-32. Patients with more than 5% residual blasts in bone marrow on day 28 receive a second course in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of cytarabine until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that which 2 of 6 patients experience dose-limiting toxicity.

Phase II: Additional patients are treated at the dose level preceding the MTD. Patients are followed monthly.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnosis of chronic myelogenous leukemia in myeloid blast crisis

    • At least 30% blasts in bone marrow
  • Philadelphia chromosome positive by cytogenetic analysis
  • bcr/abl translocation by fluorescent in situ hybridization
  • Ineligible for or refused allogeneic stem cell transplantation
  • Not previously treated with imatinib mesylate OR currently receiving imatinib mesylate with stable disease on 2 bone marrow biopsies at least 2 weeks apart
  • Performance status - ECOG 0-2
  • See Disease Characteristics
  • Bilirubin less than 3 times upper limit of normal (ULN)
  • AST and ALT less than 3 times ULN
  • Creatinine less than 2 times ULN
  • No New York Heart Association class III or IV heart disease
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective barrier contraception during and for at least 2 weeks after study for female patients and at least 3 months after study for male patients
  • See Disease Characteristics
  • No prior allogeneic bone marrow or peripheral blood stem cell transplantation
  • At least 48 hours since prior interferon alfa
  • At least 24 hours since prior hydroxyurea
  • At least 6 weeks since prior busulfan
  • No other prior chemotherapy for blast crisis (except hydroxyurea)
  • Concurrent hydroxyurea or anagrelide for severe leukocytosis or thrombocytosis allowed
  • At least 4 weeks since prior investigational agents
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00015834

Locations
United States, California
University of California at Los Angeles (UCLA )
Los Angeles, California, United States, 90095
Sponsors and Collaborators
Investigators
Principal Investigator: Ronald Paquette University of California at Los Angeles (UCLA )
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00015834     History of Changes
Other Study ID Numbers: NCI-2012-02374, UCLA-0011009, CDR0000068441
Study First Received: May 6, 2001
Last Updated: January 23, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Leukemia, Myeloid
Leukemia
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Blast Crisis
Neoplasms by Histologic Type
Neoplasms
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases
Cell Transformation, Neoplastic
Carcinogenesis
Neoplastic Processes
Pathologic Processes
Cytarabine
Imatinib
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Protein Kinase Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on September 18, 2014